Technical note: Impact of dose voxel kernel (DVK) values on dosimetry estimates in 177 Lu and 90 Y radiopharmaceutical therapy (RPT) applications.

BACKGROUND: Radiopharmaceutical therapy (RPT) is an increasingly adopted modality for treating cancer. There is evidence that the optimization of the treatment based on dosimetry can improve outcomes. However, standardization of the clinical dosimetry workflow still represents a major effort. Among the many sources of variability, the impact of using different Dose Voxel Kernels (DVKs) to generate absorbed dose (AD) maps by convolution with the time-integrated activity (TIA) distribution has not been systematically investigated. PURPOSE: This study aims to compare DVKs and assess the differences in the ADs when convolving the same TIA map with different DVKs. METHODS: DVKs of 3 × 3 × 3 mm3 sampling-nine for 177 Lu, nine for 90 Y-were selected from those most used in commercial/free software or presented in prior publications. For each voxel within a 11 × 11 × 11 matrix, the coefficient of variation (CoV) and the percentage difference between maximum and minimum values (% maximum difference) were calculated. The total absorbed dose per decay (SUM), calculated as the sum of all the voxel values in each kernel, was also compared. Publicly available quantitative SPECT images for two patients treated with 177 Lu-DOTATATE and PET images for two patients treated with 90 Y-microspheres were used, including organs at risk (177 Lu: kidneys; 90 Y: liver and healthy liver) and tumors' segmentations. For each patient, the mean AD to the volumes of interest (VOIs) was calculated using the different DVKs, the same TIA map and the same software tool for dose convolution, thereby focusing on the DVK impact. For each VOI, the % maximum difference of the mean AD between maximum and minimum values was computed. RESULTS: The CoV (% maximum difference) in voxels of normalized coordinates [0,0,0], [0,1,0], and [0,1,1] were 5%(21%), 9%(35%), and 10%(46%) for the 177 Lu DVKs. For the case of 90 Y, these values were 2%(9%), 4%(14%), and 4%(16%). The CoV (% maximum difference) for SUM was 9%(33%) for 177 Lu, and 4%(15%) for 90 Y. The variability of the mean tumor and organ AD was up to 19% and 15% in 177 Lu-DOTATATE and 90 Y-microspheres patients, respectively. CONCLUSIONS: This study showed a considerable AD variability due exclusively to the use of different DVKs. A concerted effort by the scientific community would contribute to decrease these discrepancies, strengthening the consistency of AD calculation in RPT.

Monte Carlo Simulations Corroborate PET-Measured Discrepancies in Activity Assessments of Commercial 90Y Vials.

In a recent multicenter study, discrepancies between PET/CT-measured activity and vendor-calibrated activity for 90Y glass and resin microspheres were found. In the present work, the origin of these discrepancies was investigated by Monte Carlo (MC) simulations. Methods: Three vial configurations, containing 90Y-chloride, 90Y-labeled glass microspheres, and 90Y-labeled resin microspheres, were modeled with GAMOS, and the electric signal generated in an activity meter was simulated. Energy deposition was scored in the activity meter-active regions and converted into electric current per unit activity. Internal bremsstrahlung (IB) photons, always accompanying ß-decay, were simulated in addition to 90Y decays. The electric current per source activity obtained for 90Y glass and resin microspheres, Iglass and Iresin, was compared in terms of relative percentage difference with that of 90Y-chloride ([Formula: see text] and [Formula: see text]) and each other (δ). The findings of this work were compared with the ones obtained through PET measurements in the multicenter study. Results: With the inclusion of IB photons as primary particles in MC simulations, the [Formula: see text] and [Formula: see text] results were 24.6% ± 3.9% and -15.0% ± 2.2%, respectively, whereas δ was 46.5% ± 1.9%, in very good agreement with the values reported in the multicenter study. Conclusion: The MC simulations performed in this study indicate that the discrepancies recently found between PET/CT-measured activity and vendor-calibrated activity for 90Y glass and resin microspheres can be attributed to differences in the geometry of the respective commercial vials and to the metrologic approach adopted for activity meter calibration with a 90Y-chloride liquid source. Furthermore, IB photons were shown to play a relevant role in determining the electric current in the activity meter.

Updating 90Y Voxel S-Values including internal Bremsstrahlung: Monte Carlo study and development of an analytical model.

PURPOSE: Internal Bremsstrahlung (IB) is a process accompanying ß-decay but neglected in Voxel S-Values (VSVs) calculation. Aims of this work were to calculate, through Monte Carlo (MC) simulation, updated 90Y-VSVs including IB, and to develop an analytical model to evaluate 90Y-VSVs for any voxel size of practical interest. METHODS: GATE (Geant4 Application for Tomographic Emission) was employed for simulating voxelized geometries of soft tissue, with voxels sides l ranging from 2 to 6 mm, in steps of 0.5 mm. The central voxel was set as a homogeneous source of 90Y when IB photons are not modelled. For each l, the VSVs were computed for 90Y decays alone and for 90Y + IB. The analytical model was then built through fitting procedures of the VSVs including IB contribution. RESULTS: Comparing GATE-VSVs with and without IB, differences between + 25% and + 30% were found for distances from the central voxel larger than the maximum ß-range. The analytical model showed an agreement with MC simulations within ± 5% in the central voxel and in the Bremsstrahlung tails, for any l value examined, and relative differences lower than ± 40%, for other distances from the source. CONCLUSIONS: The presented 90Y-VSVs include for the first time the contribution due to IB, thus providing a more accurate set of dosimetric factors for three-dimensional internal dosimetry of 90Y-labelled radiopharmaceuticals and medical devices. Furthermore, the analytical model constitutes an easy and fast alternative approach for 90Y-VSVs estimation for non-standard voxel dimensions.

Internal Bremsstrahlung, the missing process in beta decay Monte Carlo simulation: The relevance in 32P Dose-Point-Kernel estimation.

PURPOSE: In nuclear medicine, Dose Point Kernels (DPKs), representing the energy deposited all around a point isotropic source, are extensively used for dosimetry and are usually obtained by Monte Carlo (MC) simulations. For beta-decaying nuclides, DPK is usually estimated neglecting Internal Bremsstrahlung (IB) emission, a process always accompanying the beta decay and consisting in the emission of photons having a continuous spectral distribution. This work aims to study the significance of IB emission for DPK estimation in the case of 32P and provide DPK values corrected for the IB photon contribution. METHODS: DPK, in terms of the scaled absorbed dose fraction, F(R/X90), was first estimated by GAMOS MC simulation using the standard beta decay spectrum of 32P, Fß(R/X90). Subsequently, an additional source term accounting for IB photons and their spectral distribution was defined and used for a further MC simulation, thus evaluating the contribution of IB emission to DPK values, Fß+IB(R/X90). The relative percent difference, δ, between the DPKs obtained by the two approaches, Fß+IB vs. Fß, was studied as a function of the radial distance, R. RESULTS: As far as the energy deposition is mainly due to the beta particles, IB photons does not significantly contribute to DPK; conversely, for larger R, Fß+IB values are higher by 30-40% than Fß. CONCLUSIONS: The inclusion of IB emission in the MC simulations for DPK estimations is recommended, as well as the use of the DPK values corrected for IB photons, here provided.

18F-PSMA-1007 salivary gland dosimetry: comparison between different methods for dose calculation and assessment of inter- and intra-patient variability.

Objective. Simplified calculation approaches and geometries are usually adopted for salivary glands (SGs) dosimetry. Our aims were (i) to compare different dosimetry methods to calculate SGs absorbed doses (ADs) following [18F]-PSMA-1007 injection, and (ii) to assess the AD variation across patients and single SG components. Approach. Five patients with prostate cancer underwent sequential positron-emission tomography/computed tomography (PET/CT) acquisitions of the head and neck, 0.5, 2 and 4 h after [18F]-PSMA-1007 injection. Parotid and submandibular glands were segmented on CT to derive SGs volumes and masses, while PET images were used to derive Time-Integrated Activity Coefficients. Average ADs to single SG components or total SG (tSG) were calculated with the following methods: (i) direct Monte Carlo simulation with GATE/GEANT4 considering radioactivity in the entire PET/CT field-of-view (MC) or in the SGs only (MCsgo); (ii) spherical model (SM) of OLINDA/EXM 2.1, adopting either patient-specific or standard ICRP89 organ masses (SMstd); (iii) ellipsoidal model (EM); (iv) MIRD approach with organS-factors from OLINDA/EXM 2.1 and OpenDose collaboration, with or without contribution from cross irradiation originating outside the SGs. The maximum percent AD difference across SG components (δmax) and across patients (Δmax) were calculated.Main results. Compared to MC, ADs to single SG components were significantly underestimated by all methods (average relative differences ranging between -11.9% and -30.5%).δmaxvalues were never below 25%. The highestδmax(=702%) was obtained with SMstd. Concerning tSG, results within 10% of the MC were obtained only if cross-irradiation from the remainder of the body or from the remainder of the head was accounted for. The Δmaxranged between 58% and 78% across patients.Significance. Simple geometrical models for SG dosimetry considerably underestimated ADs compared to MC, particularly if neglecting cross-irradiation from neighboring regions. Specific masses of single SG components should always be considered given their large intra- and inter-patient variability.

Technical note: The contribution of internal bremsstrahlung to the 90 Y dose point kernel.

BACKGROUND: Internal dosimetry has an increasing role in the planning and verification of nuclear medicine therapies with radiopharmaceuticals. Dose Point Kernels (DPKs), quantifying the energy deposition all around a point source, in a homogenous medium, are extensively used for 3D dosimetry and nowadays are mostly evaluated by Monte Carlo (MC) simulation. To our knowledge, DPK for beta emitters is estimated neglecting the continuous photon emission due to the Internal Bremsstrahlung (IB), whose contribution to the absorbed dose can be relevant beyond the maximum range of betas, as evidenced in recent works. PURPOSE: Aim of this study was to investigate and quantify, by means of MC simulations, the contribution of IB photons to DPK calculated for 90 Y and provide the updated 90 Y DPK. METHODS: The overall radiation due to the decay of a 90 Y point source, placed at the centre of concentric water shells of increasing radii from 0.02 cm to 20 cm, was simulated with GAMOS, including the IB source term whose spectral distribution was described by an analytical model. Energy deposition was scored in the shells as a function of the distance from the source, R, and DPK was estimated in terms of the scaled absorbed dose fraction, F(R/X90 ), where X90 is the range within which the beta particles deposit 90% of their energy. RESULTS: A comparison between the two simulated absorbed dose distributions, calculated with or without IB, clearly shows that the latter (incomplete) choice is consistent with the findings of other Authors and systematically underestimates the absorbed dose imparted to the tissue. 90 Y DPK values currently used are underestimated by 20%-34% for R>2X90 . CONCLUSIONS: The revised values provided in this work suggest that the inclusion of IB emission in DPK evaluations is advisable for pure beta emitters.

An analytic model to calculate voxel s-values for177Lu.

Objective.177Lu is one of the most employed isotopes in targeted radionuclide therapies and theranostics, and 3D internal dosimetry for such procedures has great importance. Voxel S-Values (VSVs) approach is widely used for this purpose, but VSVs are available for a limited number of voxel dimensions. The aim of this work is to develop an analytic model for the calculation of177Lu-VSVs in any cubic voxelized geometry of practical interest.Approach. Monte Carlo (MC) simulations were implemented with the toolkit GAMOS to evaluate VSVs in voxelized geometries of soft tissue from a source of177Lu homogeneously distributed in the central voxel. Nine geometric setups, containing 15 × 15 × 15 cubic voxels of sideslranging from 2 mm to 6 mm, in steps of 0.5 mm, were considered. For eachl, the VSVs computed as a function of the 'normalized radius',Rn= R/l(withR = distance from the center of the source voxel), were fitted with a parametric function. The dependencies of the parameters as a function oflwere then fitted with appropriate functions, in order to implement the model for deducing177Lu-VSVs for anylwithin the aforementioned range.Main results. The MC-derived VSVs were satisfactorily compared with literature data for validation, and the VSVs computed with the analytic model agree with the MC ones within 2% forRn≤ 2 and within 6% forRn> 2.Significance. The proposed model enables the easy and fast calculation, with a simple spreadsheet, of177Lu-VSVs in any cubic voxelized geometry of practical interest, avoiding the necessity of implementingad-hocMC simulations to estimate VSVs for specific voxel dimensions not available in literature data.

Relevance of artefacts in99mTc-MAA SPECT scans on pre-therapy patient-specific90Y TARE internal dosimetry: a GATE Monte Carlo study.

Objective.The direct Monte Carlo (MC) simulation of radiation transport exploiting morphological and functional tomographic imaging as input data is considered the gold standard for internal dosimetry in nuclear medicine, and it is increasingly used in studies regarding trans-arterial radio-embolization (TARE). However, artefacts affecting the functional scans, such as reconstruction artefacts and motion blurring, decrease the accuracy in defining the radionuclide distribution in the simulations and consequently lead to errors in absorbed dose estimations. In this study, the relevance of such artefacts in patient-specific three-dimensional MC dosimetry was investigated in three cases of90Y TARE.Approach.The pre-therapy99mTc MacroAggregate Albumin (Tc-MAA) SPECTs and CTs of patients were used as input for simulations performed with the GEANT4-based toolkit GATE. Several pre-simulation SPECT-masking techniques were implemented, with the aim of zeroing the decay probability in air, in lungs, or in the whole volume outside the liver.Main results.Increments in absorbed dose up to about +40% with respect to the native-SPECT simulations were found in liver-related volumes of interest (VOIs), depending on the masking procedure adopted. Regarding lungs-related VOIs, decrements in absorbed doses in right lung as high as -90% were retrieved.Significance.These results highlight the relevant influence of SPECT artefacts, if not properly treated, on dosimetric outcomes for90Y TARE cases. Well-designed SPECT-masking techniques appear to be a promising way to correct for such misestimations.

Simplified patient-specific renal dosimetry in 177Lu therapy: a proof of concept.

PURPOSE: The aim of this proof-of-concept study is to propose a simplified personalized kidney dosimetry procedure in 177Lu peptide receptor radionuclide therapy (PRRT) for neuroendocrine tumors and metastatic prostate cancer. It relies on a single quantitative SPECT/CT acquisition and multiple radiometric measurements executed with a collimated external probe, properly directed on kidneys. METHODS: We conducted a phantom study involving external count-rate measurements in an abdominal phantom setup filled with activity concentrations of 99mTc, reproducing patient-relevant organ effective half-lives occurring in 177Lu PRRT. GATE Monte Carlo (MC) simulations of the experiment, using 99mTc and 177Lu as sources, were performed. Furthermore, we tested this method via MC on a clinical case of 177Lu-DOTATATE PRRT with SPECT/CT images at three time points (2, 20 and 70 hrs), comparing a simplified kidney dosimetry, employing a single SPECT/CT and probe measurements at three time points, with the complete MC dosimetry. RESULTS: The experimentally estimated kidney half-life with background subtraction applied was compatible within 3% with the expected value. The MC simulations of the phantom study, both with 99mTc and 177Lu, confirmed a similar level of accuracy. Concerning the clinical case, the simplified dosimetric method led to a kidney dose estimation compatible with the complete MC dosimetry within 6%, 12% and 2%, using respectively the SPECT/CT at 2, 20 and 70 hrs. CONCLUSIONS: The proposed simplified procedure provided a satisfactory accuracy and would reduce the imaging required to derive the kidney absorbed dose to a unique quantitative SPECT/CT, with consequent benefits in terms of clinic workflows and patient comfort.

Relevance of Internal Bremsstrahlung photons from 90Y decay: an experimental and Monte Carlo study.

Internal Bremsstrahlung (IB) is a continuous electromagnetic radiation accompanying beta decay; however, this process is not considered in radiation protection studies, particularly when estimating exposure from beta-decaying radionuclides. The aims of the present work are: i) to show that neglecting the IB process in Monte Carlo (MC) simulation leads to an underestimation of the energy deposited in a ionization chamber, in the case of a high-energy pure beta emitter such as Yttrium-90 (90Y), and ii) to determine the most reliable choice of source term for 90Y IB to be used in MC simulations. For this radionuclide, commonly employed in nuclear medicine and radiochemistry applications, experimental data acquired with a well ionization chamber have been compared with Monte Carlo (MC) calculations carried out in the GAMOS framework. Simulations that do not include the effect of the IB process, are found to give results underestimating the experimental values by 12-14%. Consequently, two models for the IB energy spectra, previously described by Italiano et al. [1], have been implemented using MC simulation and a good agreement has been achieved with one of them. We therefore conclude that inclusion of IB process in Monte Carlo simulation packages is advisable for a more accurate and complete treatment of electromagnetic interactions.

Monte Carlo 90Y PET/CT dosimetry of unexpected focal radiation-induced lung damage after hepatic radioembolisation.

Transarterial radioembolization (TARE) with 90Y-loaded microspheres is an established therapeutic option for inoperable hepatic tumors. Increasing knowledge regarding TARE hepatic dose-response and dose-toxicity correlation is available but few studies have investigated dose-toxicity correlation in extra-hepatic tissues. We investigated absorbed dose levels for the appearance of focal lung damage in a case of off-target deposition of 90Y microspheres and compared them with the corresponding thresholds recommended to avoiding radiation induced lung injury following TARE. A 64-year-old male patient received 1.6 GBq of 90Y-labelled glass microspheres for an inoperable left lobe hepatocellular carcinoma. A focal off-target accumulation of radiolabeled microspheres was detected in the left lung upper lobe at the post-treatment 90Y-PET/CT, corresponding to a radiation-induced inflammatory lung lesion at the 3-months 18F-FDG PET/CT follow-up. 90Y-PET/CT data were used as input for Monte-Carlo based absorbed dose estimations. Dose-volume-histograms were computed to characterize the heterogeneity of absorbed dose distribution. The dose level associated with the appearance of lung tissue damage was estimated as the median absorbed dose measured at the edge of the inflammatory nodule. To account for respiratory movements and possible inaccuracy of image co-registration, three different methods were evaluated to define the irradiated off-target volume. Monte Carlo-derived absorbed dose distribution showed a highly heterogeneous absorbed dose pattern at the site of incidental microsphere deposition (volume = 2.13 ml) with a maximum dose of 630 Gy. Absorbed dose levels ranging from 119 Gy to 133 Gy, were estimated at the edge of the inflammatory nodule, depending on the procedure used to define the target volume. This report describes an original Monte Carlo based patient-specific dosimetry methodology for the study of the radiation-induced damage in a focal lung lesion after TARE. In our patient, radiation-induced focal lung damage occurred at significantly higher absorbed doses than those considered for single administration or cumulative lung dose delivered during TARE.

Enhancement of radiation exposure risk from ß-emitter radionuclides due to Internal Bremsstrahlung effect: A Monte Carlo study of 90Y case.

Employment of ß-decaying radionuclides, used in many fields (industrial, clinical, research) requires a correct assessment of the operators' radiological exposure. Usually, in the dosimetric evaluation, the contribution coming from Internal Bremsstrahlung (IB) accompanying the ß-decay is not kept into account; nevertheless, this negligibility does not always appear justified, at least for high-energy ß-emitters. By means of Monte Carlo (MC) simulations, we showed how the contribution from IB photons is noteworthy for the evaluation of the overall radiation absorbed dose in the case of 90Y source. We evaluated an increase of the absorbed doses, respectively for a point source and the considered receptacles, up to + 34% and + 60% or + 15% and + 28%, depending on the adopted model of IB spectrum. These results demonstrate the relevance of IB phenomenon in radiation protection estimations and suggest extending future theoretical and experimental studies to other ß-decaying radionuclides.

Effect of granulocyte colony-stimulating factor on bone marrow: evaluation by intravoxel incoherent motion and dynamic contrast-enhanced magnetic resonance imaging.

OBJECTIVE: To report our experience with the use of intravoxel incoherent motion (IVIM) magnetic resonance imaging (MRI) and dynamic contrast-enhanced (DCE)-MRI in bone marrow before and after administration of granulocyte colony-stimulating factor (GCSF). Moreover, a small series of patients with bone metastases from breast cancer have been evaluated by IVIM DW-MRI and DCE-MRI before and after GCSF administration. MATERIALS AND METHODS: We studied with IVIM-MRI and DCE-MRI 14 patients with rectal or uterine cervix cancer studied before and 4-18 days after administration of GCSF; the second MR examination was obtained after three chemotherapy courses. IVIM perfusion fraction (f), pseudo-diffusion coefficient (D*), true diffusion coefficient (D) and apparent diffusion coefficient (ADC) as well area under the curve at 60 s (AUC60) were calculated for bone marrow before and after GCSF administration. Moreover, two different IVIM parametric maps (i.e., ADC and ADClow) were generated by selecting two different intervals of b values (0-1000 and 0-80, respectively). Furthermore, four patients affected by pelvic bone metastases from breast adenocarcinoma who received GCSF administration were also qualitatively evaluated for evidence of lesions on ADC maps, ADClow maps and DCE-MRI. RESULTS: ADC, D, D*, f and AUC60 values were significantly higher in hyperplastic bone marrow than in untreated bone marrow (p values < 0.0001, < 0.0001, < 0.001, < 0.001, < 0.0001, respectively). All bone metastases were clearly differentiable from hyperplastic bone marrow on ADClow maps, but not on ADC maps and DCE-MRI. CONCLUSION: MR functional imaging techniques, such as DW-, IVIM DW- and DCE-MRI are effective tools in assessing the response of bone marrow to the administration of growth factors. Although an overlap between signal of hyperplastic bone marrow and lytic bone metastases can occur on ADC maps and DCE-MRI, evaluation of ADClow maps by IVIM DW-MRI could permit to differentiate hyperplastic bone marrow from lytic bone metastases. Further studies are needed to confirm our data.

Internal dosimetry for TARE therapies by means of GAMOS Monte Carlo simulations.

Three-dimensional internal dosimetry is increasingly used in planning Trans-Arterial Radio-Embolization (TARE) of HepatoCellular Carcinoma (HCC). Among the existing calculation approaches, Monte Carlo (MC) simulation is the gold standard. Aim of this work was to carry out a retrospective study of clinical cases of TARE to compare the performances of different computation approaches. We developed a procedure exploiting GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations) MC. Three dimensional absorbed dose maps, dose profiles and Dose Volume Histograms (DVHs) were produced for liver through MC simulations and convolution method implemented in STRATOS software. We compared the average absorbed doses with results of Medical International Radiation Dose (MIRD) approach. For most patients, a reasonable agreement was found, with relative differences in mean doses within (-20.2%,+15.6%) for MIRD vs. MC and (-12.1%, +7.6%) for STRATOS vs. MC. Discrepancies can mainly be related to the gamma-rays contribution, more precisely taken into account in MC. For one patient we evaluated through MC simulation a lung dose of about 2 Gy coming from pulmonary shunt (96%) and from irradiation from liver (4%), with values up to 4.5 Gy near liver-lung interface. 3D dosimetry for TARE treatments can be satisfactorily carried out with convolution methods as long as VOIs of regular shape are considered. MC simulations are more appropriate for VOIs where the contribution from gamma-rays has to be carefully taken into account. The absorbed dose distribution in presence of relevant tissue inhomogeneities can be assessed accurately by means of MC simulations only.

Internal radiation dosimetry of a 152Tb-labeled antibody in tumor-bearing mice.

BACKGROUND: Biodistribution studies based on organ harvesting represent the gold standard pre-clinical technique for dose extrapolations. However, sequential imaging is becoming increasingly popular as it allows the extraction of longitudinal data from single animals, and a direct correlation with deterministic radiation effects. We assessed the feasibility of mouse-specific, microPET-based dosimetry of an antibody fragment labeled with the positron emitter 152Tb [(T1/2 = 17.5 h, Eß+mean = 1140 keV (20.3%)]. Image-based absorbed dose estimates were compared with those obtained from the extrapolation to 152Tb of a classical biodistribution experiment using the same antibody fragment labeled with 111In. 152Tb was produced by proton-induced spallation in a tantalum target, followed by mass separation and cation exchange chromatography. The endosialin-targeting scFv78-Fc fusion protein was conjugated with the chelator p-SCN-Bn-CHX-A"-DTPA, followed by labeling with either 152Tb or 111In. Micro-PET images of four immunodeficient female mice bearing RD-ES tumor xenografts were acquired 4, 24, and 48 h after the i.v. injection of 152Tb-CHX-DTPA-scFv78-Fc. After count/activity camera calibration, time-integrated activity coefficients (TIACs) were obtained for the following compartments: heart, lungs, liver, kidneys, intestines, tumor, and whole body, manually segmented on CT. For comparison, radiation dose estimates of 152Tb-CHX-DTPA-scFv78-Fc were extrapolated from mice dissected 4, 24, 48, and 96 h after the injection of 111In-CHX-DTPA-scFv78-Fc (3-5 mice per group). Imaging-derived and biodistribution-derived organ TIACs were used as input in the 25 g mouse model of OLINDA/EXM® 2.0, after appropriate mass rescaling. Tumor absorbed doses were obtained using the OLINDA2 sphere model. Finally, the relative percent difference (RD%) between absorbed doses obtained from imaging and biodistribution were calculated. RESULTS: RD% between microPET-based dosimetry and biodistribution-based dose extrapolations were + 12, - 14, and + 17 for the liver, the kidneys, and the tumors, respectively. Compared to biodistribution, the imaging method significantly overestimates the absorbed doses to the heart and the lungs (+ 89 and + 117% dose difference, respectively). CONCLUSIONS: MicroPET-based dosimetry of 152Tb is feasible, and the comparison with organ harvesting resulted in acceptable dose discrepancies for body districts that can be segmented on CT. These encouraging results warrant additional validation using radiolabeled biomolecules with a different biodistribution pattern.

Recombinant human thyrotropin (rhTSH) versus Levo-thyroxine withdrawal in radioiodine therapy of differentiated thyroid cancer patients: differences in abdominal absorbed dose.

PURPOSE: In DTC patients, 131-radioiodine therapy has routinely been used for many years for thyroid remnant ablation after thyroid surgery. To date, two different strategies can be used to achieve sufficient TSH stimulation on thyroid remnant: (I) Levo-thyroxine withdrawal or (II) rhTSH stimulation. The aim of our study was to compare the abdominal absorbed dose ratio between differentiated thyroid cancer patients who underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. METHODS: We reviewed the records of 63 patients affected by differentiated thyroid cancer. All patients underwent thyroid remnant ablation after either L-T4 withdrawal or rhTSH stimulation. A post-therapy whole-body scan was obtained 5 days after 131-radioiodine therapy. Qualitative and quantitative image analysis was performed. Quantitative analysis was performed by drawing seven regions of interest on the abdomen (anterior and posterior views) to estimate both the activity ratio (AR) and absorbed dose ratio (DR) obtained in patients treated in hypothyroidism or after rhTSH stimulation. RESULTS: The values of the activity and absorbed dose ratios obtained on each abdomen region (liver, stomach, ascending colon, transverse colon, descending colon, rectum, and small intestine) were always higher in patients treated after L-T4 withdrawal than after rhTSH stimulation with p-values of 0.000, 0.000, 0.001, 0.000, 0.022, 0.007, and 0.002, respectively. CONCLUSIONS: DTC patients treated with 131-radioiodine after rhTSH stimulation have lower abdominal radioiodine activity than hypothyroid patients. Our data could be of practical relevance in terms of patient management. The potential impact on rare radioiodine-related gastrointestinal side effects is to be established in specifically designed prospective studies.

Effect of Beta Particles Spectrum on Absorbed Fraction in Internal Radiotherapy.

OBJECTIVES: The purpose of this research is to study the effect of beta spectrum on absorbed fraction (ϕ) and to find suitable analytical functions for beta spectrum absorbed fractions in spherical and ellipsoidal volumes with a uniform distribution for several radionuclides that are commonly used in nuclear medicine. METHODS: In order to obtain the beta particle absorbed fraction, Monte Carlo simulations were performed by using the MCNPX code. The validation of the simulations was performed by calculating the absorbed fractions in spheres and comparing the results with the data published by other investigators. The absorbed fractions were calculated and compared by using an actual beta energy spectrum with those obtained through the mean beta energy of 14C, 199Au, 177Lu, 131I, 90Sr, 153Sm, 186Re, 32P, 90Y, 38Cl and 88Rb radionuclides. RESULTS: The maximum difference between the absorbed fractions for beta particles accounting for the whole beta spectrum of all the considered nuclides was 29.62% with respect to the mean beta energy case. Suitable analytical relationships were found between the absorbed fraction and the generalized radius, and the dependence of the fitting parameters from beta spectrum energy was discussed and fitted by appropriate parametric functions. CONCLUSION: The results allowed the calculation of the absorbed fractions from the above stated beta sources uniformly distributed in spherical and ellipsoidal volumes of any ellipticity and volume, in a wide range of practical volumes that are not only used for internal dosimetry in nuclear medicine applications, but also in radiological protection estimates of doses from internal contamination.

A Monte Carlo model for the internal dosimetry of choroid plexuses in nuclear medicine procedures.

Choroid plexuses are vascular structures located in the brain ventricles, showing specific uptake of some diagnostic and therapeutic radiopharmaceuticals currently under clinical investigation, such as integrin-binding arginine-glycine-aspartic acid (RGD) peptides. No specific geometry for choroid plexuses has been implemented in commercially available software for internal dosimetry. The aims of the present study were to assess the dependence of absorbed dose to the choroid plexuses on the organ geometry implemented in Monte Carlo simulations, and to propose an analytical model for the internal dosimetry of these structures for 18F, 64Cu, 67Cu, 68Ga, 90Y, 131I and 177Lu nuclides. A GAMOS Monte Carlo simulation based on direct organ segmentation was taken as the gold standard to validate a second simulation based on a simplified geometrical model of the choroid plexuses. Both simulations were compared with the OLINDA/EXM sphere model. The gold standard and the simplified geometrical model gave similar dosimetry results (dose difference < 3.5%), indicating that the latter can be considered as a satisfactory approximation of the real geometry. In contrast, the sphere model systematically overestimated the absorbed dose compared to both Monte Carlo models (range: 4-50% dose difference), depending on the isotope energy and organ mass. Therefore, the simplified geometric model was adopted to introduce an analytical approach for choroid plexuses dosimetry in the mass range 2-16 g. The proposed model enables the estimation of the choroid plexuses dose by a simple bi-parametric function, once the organ mass and the residence time of the radiopharmaceutical under investigation are provided.

Radiation protection from external exposure to radionuclides: A Monte Carlo data handbook.

The availability of a resource collecting dose factors for the evaluation of the absorbed doses from external exposure during the manipulation of radioactive substances is fundamental for radiological protection purposes. Monte Carlo simulations are useful for the accurate calculation of dose distributions in complex geometries, particularly in presence of extended spectra of multi-radiation sources. We considered, as possible irradiation scenarios, a point source, a uniform planar source resembling a contaminated surface, several source volumes contained in plastic or glass receptacles, and the direct skin contamination case, implementing the corresponding Monte Carlo simulations in GAMOS (GEANT4-based Architecture for Medicine-Oriented Simulations). A set of 50 radionuclides was studied, focusing the attention on those ones mainly used in nuclear medicine, both for diagnostic and therapeutic purposes, in nuclear physics laboratories and for instrument calibration. Skin dose equivalents at 70 µm of depth and deep dose equivalents at 10 mm of depth are reported for different configurations and organized in easy-to-read tables.